Medline ® Abstracts for References 89,90

BACKGROUND: Reducing the actions of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors (ACEIs) slows nephropathy progression in patients with or without diabetes. Post hoc analyses of many ACEI-based clinical trials demonstrate the greatest slowing of renal disease progression in patients with the greatest degree of renal insufficiency at study initiation. However, many physicians fail to use ACEIs or angiotensin receptor blockers in patients with renal insufficiency for fear that either serum creatinine or potassium levels will rise.

OBJECTIVE: To determine if limited initial reduction in either glomerular filtration rate (GFR) or elevation in serum creatinine levels, associated with ACEI or angiotensin receptor blocker use, results in long-term protection against decline in renal function in patients with renal insufficiency.

METHODS: We reviewed 12 randomized clinical trials that evaluated renal disease progression among patients with preexisting renal insufficiency. Six of these studies were multicenter, double-blinded,and placebo controlled, with the remainder being smaller randomized studies with a minimum 2-year follow-up on renal function. These investigations evaluated patients with and without diabetes or systolic heart failure. Average duration of follow-up for all studies was 3 years. Trials were examined in the context of changes in either serum creatinine levels or GFR in the group randomized to an ACEI (N = 1,102). Sixty-four percent of these individuals (705/1,102) had renal function data at both less than 6 months and at the end of the study.

RESULTS: Most trials demonstrated that patients with preexisting renal insufficiency manifested an acute fall in GFR, a rise in serum creatinine, or both. Those randomized to an ACEI with a serum creatinine level of 124 pmol/L or greater (>or =1.4 mg/dL) demonstrated a 55% to 75% risk reduction in renal disease progression compared with those with normal renal function randomized to an ACEI. An inverse correlation was observed between the amount of renal function loss at baseline and the subsequent rate of annual decline in renal function following randomization to an antihypertensive regimen that contained an ACEI.

CONCLUSIONS: A strong association exists between acute increases in serum creatinine of up to 30% that stabilize within the first 2 months of ACEI therapy and long-term preservation of renal function. This relationship holds for persons with creatinine values of greater than 124 pmol/L (>1.4 mg/dL). Thus, withdrawal of an ACEI in such patients should occur only when the rise in creatinine exceeds 30% above baseline within the first 2 months of ACEI initiation, or hyperkalemia develops, ie, serum potassium level of 5.6 mmol/L or greater.

"The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or<130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.